Abstract

B107

In order to investigate the molecular causes underlying these breast cancer disparities between African American women and European American women we have conducted studies to elucidate biological differences in tumors which may influence clinical outcomes between these ethnic populations. The disparities that exist in breast cancer mortality rates between ethnic groups have traditionally been attributed to socioeconomic inequities which reflect access to health care. Recent studies however suggest that the disparities are not only due to factors of health care treatment, but potential differences in the biology of the tumors among different ethnic groups. These differences implicate probable genetic and/or epigenetic factors at work. African and African-American women have been shown to be more likely to present with breast cancer at relatively younger ages, and their specific tumor types are more likely to be triple negative (Estrogen Receptor, Her2/Neu, Progesterone Receptor) extremely aggressive and more difficult detect early or even treat successfully with current methods. We used computational data mining to establish a list of epigenetic factors which show distinct expression patterns in ER negative breast cancer samples. Then have conducted Tissue Microarray (TMA) immunohistical staining of a chromatin factor that may have interesting implications in the progression of aggressive breast cancer. We have discovered a correlation of increasing protein levels of this factor with increasing grade of tumor types and decreasing survival rates. A subsequent search of functionally relevant polymorphisms within the enhancer region of the chromatin factor gene revealed a single nucleotide polymorphism (SNP) which varies significantly in frequency between African and European populations. This SNP creates a novel binding site for transcription factors that have been shown to be upregulated specifically in ER negative breast cancer types relative to ER positive breast cancer. These findings suggest that altered regulation of the chromatin factor occurs more commonly within populations enriched for this enhancer region SNP and this may create a context for a more aggressive cancer. We are currently genotyping this and other SNPs in our breast cancer cases and controls to provide further support for the correlation of this chromatin factor with aggressiveness in ER negative tumors. Ultimately, the findings from this study will lay the groundwork for building a larger research project to better detect epigenetic factors that influence unique breast cancer types in specific populations from common ancestral descent. Additionally, these findings will also provide better insight into the molecular epigenetic pathways that are affected during the progression of cancer in general in all populations, thereby providing new research tools to created tailored cancer treatment options.

Footnotes

First AACR International Conference on the Science of Cancer Health Disparities-- Nov 27-30, 2007; Atlanta, GA